Pulsatile and nocturnal growth hormone secretions in men do not require periodic declines of somatostatin

• Published in: American journal of physiology: endocrinology and metabolism 2003-07, Vol.285 (1), p.E163-E170
• Main Authors: Dimaraki, Eleni V, Jaffe, Craig A, Bowers, Cyril Y, Marbach, Peter, Barkan, Ariel L
• Format: Article
• Language: English
• Subjects: Adult; Circadian Rhythm - physiology; Growth Hormone-Releasing Hormone - pharmacology; Hormones - administration & dosage; Hormones - pharmacokinetics; Hormones - pharmacology; Human Growth Hormone - blood; Humans; Infusions, Intravenous; Male; Octreotide - administration & dosage; Octreotide - pharmacokinetics; Octreotide - pharmacology; Oligopeptides - pharmacology; Somatostatin - blood; Somatostatin - physiology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00334.2002

1 Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan, and 2 Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48109; 3 Department of Internal Medicine, Division of Endocrinology and Metabolism, Tulane University, New Orleans, Louisiana 70112; and 4 Novartis Pharma Ltd., CH-4002 Basel, Switzerland Submitted 24 July 2002 ; accepted in final form 23 March 2003 Using a continuous subcutaneous octreotide infusion to create constant supraphysiological somatostatinergic tone, we have previously shown that growth hormone (GH) pulse generation in women is independent of endogenous somatostatin (SRIH) declines. Generalization of these results to men is problematic, because GH regulation is sexually dimorphic. We have therefore studied nine healthy young men (age 26 ± 6 yr, body mass index 23.3 ± 1.2 kg/m 2 ) during normal saline and octreotide infusion (8.4 µg/h) that provided stable plasma octreotide levels (764.5 ± 11.6 pg/ml). GH was measured in blood samples obtained every 10 min for 24 h. Octreotide suppressed 24-h mean GH by 52 ± 13% ( P = 0.016), GH pulse amplitude by 47 ± 12% ( P = 0.012), and trough GH by 39 ± 12% ( P = 0.030), whereas GH pulse frequency and the diurnal rhythm of GH secretion remained essentially unchanged. The response of GH to GH-releasing hormone (GHRH) was suppressed by 38 ± 15% ( P = 0.012), but the GH response to GH-releasing peptide-2 was unaffected. We conclude that, in men as in women, declines in hypothalamic SRIH secretion are not required for pulse generation and are not the cause of the nocturnal augmentation of GH secretion. We propose that GH pulses are driven primarily by GHRH, whereas ghrelin might be responsible for the diurnal rhythm of GH. somatotropin; pulsatility; diurnal rhythm; octreotide; ghrelin; somatotropin-releasing hormone Address for reprint requests and other correspondence: A. L. Barkan, 3920 Taubman Center, Box 0354, Ann Arbor, MI 48109–0354 (E-mail: abarkan{at}umich.edu ).